The overall objective of this application is to develop a specific and simple diagnostic test to identify individuals infected with Mycobacterium leprae and therefore sources of continuing new case detection, enabling rational chemoprophylaxis of leprosy leading not only to decrease in infectious burden but in reductions in nerve damage and disabilities. We hypothesize that such a diagnostic test can be achieved by measuring the immunologic response patterns to specific M. leprae antigens in peripheral blood samples from patients and contacts. The specific aims of this proposal are to: 1) develop a specific and simple first generation diagnostic test using advanced bioinformatics to identify M. leprae-specific peptides predicted to bind to 11 major HLA-DR alleles and to activate T-cell release of IFN-, to be incorporated into the QuantiFERON(R) platform; 2) To identify novel M. leprae antigens, including glycoproteins and lipoglycoproteins, that trigger innate and acquired immune responses during infection; and, 3) to develop an advanced integrated microfluidics-based portable diagnostic test to simultaneously measure multiple immunologic parameters providing enhanced specificity, sensitivity, and, perhaps, predictions of disease. The proposed experimental strategy will ensure development of a portable, state-of-the-art diagnostic test to detect M. leprae infection, identify sources of continuing new cases but also a new technology platform that can be readily adapted to implementation in leprosy endemic areas and to other neglected tropical infectious diseases. H Leprosy continues as a major health and economic burden in developing countries. We propose to develop a microfluidics-based portable diagnostic test to allow diagnosis of infection and sources of continuing transmission, allowing informed chemoprophylaxis and thereby further reduction in the global leprosy burden including disease complications including permanent damage to the skin, nerves, limbs and eyes.